ArticleGenes & development2013
Tissue-specific splicing of a ubiquitously expressed transcription factor is essential for muscle differentiation.
Article in Genes & development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
72 citing papers in PubMed, 128 citations in OpenAlex.
- BRD4 directs myofiber identity and metabolic adaptation through CHD4 cooperation.Nature communications · 2026Article
- Enhancer regulator MLL4 controls skeletal muscle metabolic efficiency by limiting AMPK-mediated fuel catabolism.Nature communications · 2025Article
- The muscle specific MEF2Dα2 isoform promotes muscle ketolysis and running capacity in mice.EMBO reports · 2025Article
- Alternative splicing ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- The Spatial-Temporal Alternative Splicing Profile Reveals the Functional Diversity of FXR1 Isoforms in Myogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Development and tissue specific expression of RAPGEF1 (C3G) transcripts having exons encoding disordered segments with predicted regulatory function.Molecular biology reports · 2024Article
- Biallelic variants in SNUPN cause a limb girdle muscular dystrophy with myofibrillar-like features.Brain : a journal of neurology · 2024Article
- Epigenetic control of skeletal muscle atrophy.Cellular & molecular biology letters · 2024Review
- Alternative splicing ofbioRxiv : the preprint server for biology · 2024Article
- Bulk and single-cell alternative splicing analyses reveal roles of TRA2B in myogenic differentiation.Cell proliferation · 2024Article
- Article
- Peak Scores Significantly Depend on the Relationships between Contextual Signals in ChIP-Seq Peaks.International journal of molecular sciences · 2024Article
- The Molecular and Biological Function of MEF2D in Leukemia.Advances in experimental medicine and biology · 2024Review
- RBFOX2 regulated EYA3 isoforms partner with SIX4 or ZBTB1 to control transcription during myogenesis.iScience · 2023Article
- Epitranscriptomics as a New Layer of Regulation of Gene Expression in Skeletal Muscle: Known Functions and Future Perspectives.International journal of molecular sciences · 2023Review
- The physiology of alternative splicing.Nature reviews. Molecular cell biology · 2023Review
- Alternatively spliced exon regulates context-dependent MEF2D higher-order assembly during myogenesis.Nature communications · 2023Article
- The identification of protein and RNA interactors of the splicing factor Caper in the adultFrontiers in molecular neuroscience · 2023Article
- RNA Transcript Diversity in Neuromuscular Research.Journal of neuromuscular diseases · 2023Review
- Comprehensive analysis of pre-mRNA alternative splicing regulated by m6A methylation in pig oxidative and glycolytic skeletal muscles.BMC genomics · 2022Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Alternate splicing contributes extensively to cellular complexity by generating protein isoforms with divergent functions. However, the role of alternate isoforms in development remains poorly understood. Mef2 transcription factors are essential transducers of cell signaling that modulate differentiation of many cell types. Among Mef2 family members, Mef2D is unique, as it undergoes tissue-specific splicing to generate a muscle-specific isoform. Since the ubiquitously expressed (Mef2Dα1) and muscle-specific (Mef2Dα2) isoforms of Mef2D are both expressed in muscle, we examined the relative contribution of each Mef2D isoform to differentiation. Using both in vitro and in vivo models, we demonstrate that Mef2D isoforms act antagonistically to modulate differentiation. While chromatin immunoprecipitation (ChIP) sequencing analysis shows that the Mef2D isoforms bind an overlapping set of genes, only Mef2Dα2 activates late muscle transcription. Mechanistically, the differential ability of Mef2D isoforms to activate transcription depends on their susceptibility to phosphorylation by protein kinase A (PKA). Phosphorylation of Mef2Dα1 by PKA provokes its association with corepressors. Conversely, exon switching allows Mef2Dα2 to escape this inhibitory phosphorylation, permitting recruitment of Ash2L for transactivation of muscle genes. Thus, our results reveal a novel mechanism in which a tissue-specific alternate splicing event has evolved that permits a ubiquitously expressed transcription factor to escape inhibitory signaling for temporal regulation of gene expression.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.